Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population
Association of common and rare variants of SCN10A gene with sudden unexplained nocturnal death syndrome in Chinese Han population
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SCN10A基因常见和罕见变异与中国汉族人群不明原因夜间死亡综合征的关联。
DOI：
10.1007/s00414-016-1397-1
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发表时间：
2017-01-01
影响因子：
2.1
通讯作者：
Cheng, Jianding
中科院分区：
文献类型：
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作者：
Zhang, Liyong;Zhou, Feng;Cheng, Jianding
不明原因夜间猝死综合征（SUNDS）对于法医病理学家和内科医生来说，仍然是一种病因不明且尸检无异常发现的病症。SUNDS幸存者的心电图（ECG）特征和临床表型强烈表明，SUNDS与 Brugada综合征（BrS）有一些相似之处。最近，钠通道Na - v 1.8编码基因SCN10A的变异被确定与BrS有关。在此，我们研究了中国汉族人群中105例散发的SUNDS患者和22例BrS病例与SCN10A基因变异的关联。在SUNDS患者中总共检测到6种罕见突变和16种多态性。在这6种罕见突变中，2种为推定的致病性突变（F386C和R1263*），1种可能是致病性突变（R14H），另外3种被预测为良性（R817Q、T1181M和P1683S）。至于16种多态性，1种是位于内含子24的新型多态性（c.4144 - 84G > A），其余的先前已有报道，包括一种多态性（c.2884A > G [I962V]），其在SUNDS组和对照组之间的等位基因频率有统计学显著差异（p = 0.044）。在BrS病例中也检测到5种罕见突变和15种多态性。这是关于中国汉族人群中SUNDS和BrS的SCN10A基因常见和罕见变异的首次报道，为SCN10A可能是SUNDS的一个新的易感基因并在中国约占SUNDS的3%提供了遗传流行病学证据。
Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unknown etiology to both forensic pathologists and physicians. The electrocardiogram (ECG) characteristics and clinical phenotype of SUNDS survivors strongly suggest that SUNDS shares some similarities with Brugada syndrome (BrS). Recently, the variants of sodium channel Na-v 1.8 coding gene SCN10A were identified to be associated with BrS. Here, we investigated the association of SCN10A gene variants with 105 sporadic SUNDS victims and 22 BrS cases in the Chinese Han population. A total of 6 rare mutations and 16 polymorphisms were detected in SUNDS victims. Of the six rare mutations, two were putative pathogenic mutations (F386C and R1263*), one was a likely pathogenic mutation (R14H), and the other three were predicted as benign (R817Q, T1181M, and P1683S). As for the 16 polymorphisms, 1 was a novel polymorphism (c.4144-84G > A) located in intron 24, and the rest were reported previously including one polymorphism (c.2884A > G [I962V]) which showed a statistically significant difference in allele frequency (p = 0.044) between SUNDS and the control group. There were also 5 rare mutations and 15 polymorphisms detected in BrS cases. This is the first report of common and rare variants of SCN10A gene in SUNDS and BrS in the Chinese Han population, which provides the genetic epidemiological evidence that SCN10A may be a novel susceptibility gene for SUNDS and account for approximately 3 % of SUNDS in China.